tbuckley/cabot-search huggingface dataset:
Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study
Authors: Alessio Gasperetti, Richard T. Carrick, Sarah Costa, Paolo Compagnucci, Laurens P. Bosman, Monica Chivulescu, Crystal Tichnell, Brittney Murray, Harikrishna Tandri, Rafik Tadros, Lena Rivard, Maarten P. van den Berg, Katja Zeppenfeld, Arthur A.M. Wilde, Giulio Pompilio, Corrado Carbucicchio, Antonio Dello Russo, Michela Casella, Anneli Svensson, Corinna B. Brunckhorst, J. Peter van Tintelen, Pyotr G. Platonov, Kristina H. Haugaa, Firat Duru, Anneline S.J.M. te Riele, Paul Khairy, Claudio Tondo, Hugh Calkins, Cynthia A. James, Ardan M. Saguner, Julia Cadrin-Tourigny
Journal: Circulation (2022)

A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value.All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period.Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value.PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.
Genetic Variants Close to <i>TTN</i> , <i>NKX2-5</i> , and <i>MYH6</i> Associate With AVNRT
Authors: Laura Andreasen, Gustav Ahlberg, Hildur M. Ægisdottir, Gardar Sveinbjörnsson, Pia R. Lundegaard, Jacob P. Hartmann, Christian Paludan-Müller, Katra Hadji-Turdeghal, Jonas Ghouse, Steen Pehrson, Henrik K. Jensen, Sam Riahi, Jim Hansen, Niels Sandgaard, Erik Sørensen, Karina Banasik, Susanne G. Sækmose, Mie T. Bruun, Henrik Hjalgrim, Christian Erikstrup, Ole B. Pedersen, Michael Wittig, Stig Haunsø, Sisse R. Ostrowski, Andre Franke, Søren Brunak, Jørgen K. Kanters, Christina Ellervik, Henning Bundgaard, Henrik Ullum, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Hilma Holm, David O. Arnar, Kari Stefansson, Jesper H. Svendsen, Morten S. Olesen
Journal: Circulation Research (2022)
H2S responsive PEGylated poly (lipoic acid) with ciprofloxacin for targeted therapy of Salmonella
Authors: Lu Han, Xu-Wei Liu, Tao Zang, Hao Ren, Dun-Sheng Liang, Shuan-Cheng Bai, Cang Li, Xiao-Ping Liao, Ya-Hong Liu, Chaoqun Zhang, Jian Sun
Journal: Journal of Controlled Release (2022)
Platform trials to overcome major shortcomings of traditional clinical trials in non-alcoholic steatohepatitis? Pros and cons
Authors: Juan M. Pericàs, Frank Tacke, Quentin M. Anstee, Nicholas A. Di Prospero, Mette Skalshøj Kjær, Peter Mesenbrink, Franz Koenig, Joan Genescà, Vlad Ratziu
Journal: Journal of Hepatology (2022)

Non-alcoholic fatty liver disease is a condition that affects 25% of the population. Non-alcoholic steatohepatitis (NASH) is a progressive form of the disease that can lead to severe complications such as cirrhosis and hepatocellular carcinoma. Despite its high prevalence, no drugs are currently approved for the treatment of NASH. The drug development pipeline in NASH is very active, yet most assets do not progress to phase III trials and those that do reach phase III often fail to achieve the endpoints necessary for approval by regulatory agencies. Amongst other reasons, the methodological and operational features of traditional clinical trials in NASH might impede optimal drug development. In this regard, platform trials might be an attractive complement or alternative to conventional clinical trials. Platform trials use a master protocol which enables evaluation of multiple investigational medicinal products concurrently or sequentially with a single, shared control arm. Through Bayesian interim analyses, these trials allow for early exit of drugs from the trial based on success or futility, while providing participants better chances of receiving active compounds through adaptive randomisation. Overall, platform trials represent an alternative for patients, pharmaceutical companies, and clinicians in the quest to accelerate the approval of pharmacologic treatments for NASH.
Low serum neutralization of Omicron variants a month after AZD7442 prophylaxis initiation
Authors: Xavier de Lamballerie, Guillaume Martin-Blondel, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Denis Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Vincent Lévy
Journal: Journal of Infection (2022)
The relationship between Post COVID symptoms in young people and their parents
Authors: Marta Bertran, Snehal M Pinto Pereira, Manjula D Nugawela, Terence Stephenson, Roz Shafran, Tamsin Ford, Marta Buszewicz, Elizabeth Whittaker, Isobel Heyman, Terry Y Segal, Emma Dalrymple, Shamez N Ladhani
Journal: Journal of Infection (2022)
CXCL16 associates with adverse outcome and cardiac involvement in hospitalized patients with Covid-19
Authors: Ida Gregersen, Thor Ueland, Jan Cato Holter, Maria Belland Olsen, Annika E Michelsen, Sarah L Murphy, Anders Aune Tveita, Katerina Nezvalova Henriksen, Hedda Hoel, Lena Bugge Nordberg, Aleksander Rygh Holten, Thor Edvardsen, Kuan Yang, Lars Heggelund, Marius Trøseid, Fredrik Müller, Anders Benjamin Kildal, Anne Ma Dyrhol-Riise, Andreas Barratt-Due, Tuva B Dahl, Pål Aukrust, Bente Halvorsen
Journal: Journal of Infection (2022)
Novel HIV-1 A6/B recombinant forms (CRF133_A6B and URF_A6/B) circulating in Krasnoyarsk region, Russia
Authors: Lada V Maksimenko, Mariya V Sivay, Alexei V Totmenin, Alexander N Shvalov, Sergey E Skudarnov, Tatyana S Ostapova, Svetlana V Yaschenko, Rinat A Maksutov, Natalya M Gashnikova
Journal: Journal of Infection (2022)
How cancer cells make and respond to interferon-I
Authors: HyeonJoo Cheon, Yuxin Wang, Samantha M. Wightman, Mark W. Jackson, George R. Stark
Journal: Trends in cancer (2022)

Acute exposure of cancer cells to high concentrations of type I interferon (IFN-I) drives growth arrest and apoptosis, whereas chronic exposure to low concentrations provides important prosurvival advantages. Tyrosine-phosphorylated IFN-stimulated gene (ISG) factor 3 (ISGF3) drives acute deleterious responses to IFN-I, whereas unphosphorylated (U-)ISGF3, lacking tyrosine phosphorylation, drives essential constitutive prosurvival mechanisms. Surprisingly, programmed cell death-ligand 1 (PD-L1), often expressed on the surfaces of tumor cells and well recognized for its importance in inactivating cytotoxic T cells, also has important cell-intrinsic protumor activities, including dampening acute responses to cytotoxic high levels of IFN-I and sustaining the expression of the low levels that benefit tumors. More thorough understanding of the newly recognized complex roles of IFN-I in cancer may lead to the identification of novel therapeutic strategies.
Addition of Niraparib to Best Supportive Care as Maintenance Treatment in Patients with Advanced Urothelial Carcinoma Whose Disease Did Not Progress After First-line Platinum-based Chemotherapy: The Meet-URO12 Randomized Phase 2 Trial
Authors: Francesca Vignani, Rosa Tambaro, Ugo De Giorgi, Patrizia Giannatempo, Davide Bimbatti, Claudia Carella, Marco Stellato, Francesco Atzori, Michele Aieta, Cristina Masini, Alketa Hamzaj, Paola Ermacora, Antonello Veccia, Giuseppa Scandurra, Teresa Gamba, Gianluca Ignazzi, Sandro Pignata, Marilena Di Napoli, Cristian Lolli, Giuseppe Procopio, Francesco Pierantoni, Antonia Zonno, Daniele Santini, Massimo Di Maio
Journal: European Urology (2022)
Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes
Authors: Peter Valent, Amy D. Klion, Florence Roufosse, Dagmar Simon, Georgia Metzgeroth, Kristin M. Leiferman, Juliana Schwaab, Joseph H. Butterfield, Wolfgang R. Sperr, Karl Sotlar, Peter Vandenberghe, Gregor Hoermann, Torsten Haferlach, Richard Moriggl, Tracy I. George, Cem Akin, Bruce S. Bochner, Jason Gotlib, Andreas Reiter, Hans‐Peter Horny, Michel Arock, Hans‐Uwe Simon, Gerald J. Gleich
Journal: Allergy (2022)

Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be "non-clonal" cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials.
Dual activation of estrogen receptor alpha and glucocorticoid receptor upregulate CRTh2‐mediated type 2 inflammation; mechanism driving asthma severity in women?
Authors: Meerah Vijeyakumaran, MohdWessam Al Jawhri, Jenna Fortunato, Lauren Solomon, Nami Shrestha Palikhe, Harissios Vliagoftis, Lisa Cameron
Journal: Allergy (2022)

Abstract Background Type 2‐high asthma is characterized by elevated levels of circulating Th2 cells and eosinophils, cells that express chemoattractant‐homologous receptor expressed on Th2 cells (CRTh2). Severe asthma is more common in women than men; however, the underlying mechanism(s) remain elusive. Here we examined whether the relationship between severe asthma and type 2 inflammation differs by sex and if estrogen influences Th2 cell response to glucocorticoid (GC). Methods Type 2 inflammation and the proportion of blood Th2 cells (CD4 + CRTh2 + ) were assessed in whole blood from subjects with asthma ( n = 66). The effects of GC and estrogen receptor alpha (ERα) agonist on in vitro differentiated Th2 cells were examined. Expression of CRTh2, type 2 cytokines and degree of apoptosis (Annexin V + , 7‐AAD) were determined by flow cytometry, qRT‐PCR, western blot and ELISA. Results In severe asthma, the proportion of circulating Th2 cells and hospitalizations were higher in women than men. Women with severe asthma also had more Th2 cells and serum IL‐13 than women with mild/moderate asthma. Th2 cells, eosinophils and CRTh2 mRNA correlated with clinical characteristics associated with asthma control in women but not men. In vitro , GC and ERα agonist treated Th2 cells exhibited less apoptosis, more CRTh2 as well as IL‐5 and IL‐13 following CRTh2 activation than Th2 cells treated with GC alone. Conclusion Women with severe asthma had higher levels of circulating Th2 cells than men, which may be due to estrogen modifying the effects of GC, enhancing Th2 cell survival and type 2 cytokine production.
Self-supervised learning enables 3D digital subtraction angiography reconstruction from ultra-sparse 2D projection views: A multicenter study
Authors: Huangxuan Zhao, Zhenghong Zhou, Feihong Wu, Dongqiao Xiang, Hui Zhao, Wei Zhang, Lin Li, Zhong Li, Jia Huang, Hongyao Hu, Chengbo Liu, Tao Wang, Wenyu Liu, Jinqiang Ma, Fan Yang, Xinggang Wang, Chuansheng Zheng
Journal: Cell Reports Medicine (2022)

3D digital subtraction angiography (DSA) reconstruction from rotational 2D projection X-ray angiography is an important basis for diagnosis and treatment of intracranial aneurysms (IAs). The gold standard requires approximately 133 different projection views for 3D reconstruction. A method to significantly reduce the radiation dosage while ensuring the reconstruction quality is yet to be developed. We propose a self-supervised learning method to realize 3D-DSA reconstruction using ultra-sparse 2D projections. 202 cases (100 from one hospital for training and testing, 102 from two other hospitals for external validation) suspected to be suffering from IAs were conducted to analyze the reconstructed images. Two radiologists scored the reconstructed images from internal and external datasets using eight projections and identified all 82 lesions with high diagnostic confidence. The radiation dosages are approximately 1/16.7 compared with the gold standard method. Our proposed method can help develop a revolutionary 3D-DSA reconstruction method for use in clinic.
The emerging role of pyroptosis in pediatric cancers: from mechanism to therapy
Authors: Hua Wang, Xiaowen Zhou, Chenbei Li, Shuxiang Yan, Chengyao Feng, Jieyu He, Zhihong Li, Chao Tu
Journal: Journal of Hematology & Oncology (2022)

Abstract Pediatric cancers are the driving cause of death for children and adolescents. Due to safety requirements and considerations, treatment strategies and drugs for pediatric cancers have been so far scarcely studied. It is well known that tumor cells tend to progressively evade cell death pathways, which is known as apoptosis resistance, one of the hallmarks of cancer, dominating tumor drug resistance. Recently, treatments targeting nonapoptotic cell death have drawn great attention. Pyroptosis, a newly specialized form of cell death, acts as a critical physiological regulator in inflammatory reaction, cell development, tissue homeostasis and stress response. The action in different forms of pyroptosis is of great significance in the therapy of pediatric cancers. Pyroptosis could be induced and consequently modulate tumorigenesis, progression, and metastasis if treated with local or systemic therapies. However, excessive or uncontrolled cell death might lead to tissue damage, acute inflammation, or even cytokine release syndrome, which facilitates tumor progression or recurrence. Herein, we aimed to describe the molecular mechanisms of pyroptosis, to highlight and discuss the challenges and opportunities for activating pyroptosis pathways through various oncologic therapies in multiple pediatric neoplasms, including osteosarcoma, neuroblastoma, leukemia, lymphoma, and brain tumors.
A risk score for identifying patients at a low risk of bacterial meningitis amongst adults with cerebrospinal fluid leucocytosis and a negative gram stain result: a derivation and validation study
Authors: Thijs M. van Soest, Liora ter Horst, Nora Chekrouni, Merijn W. Bijlsma, Matthijs C. Brouwer, Daniela Urueta Portillo, Diederik van de Beek, Rodrigo Hasbun
Journal: Clinical Microbiology and Infection (2022)
<scp>12‐HETE</scp> promotes late‐phase responses in a murine model of allergic rhinitis
Authors: Tatsuro Nakamura, Yuri Tachibana, Takahisa Murata
Journal: Allergy (2022)

Appendix S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mitochondrial quality control proteases and their modulation for cancer therapy
Authors: Jiangnan Zhang, Wenliang Qiao, Youfu Luo
Journal: Medicinal Research Reviews (2022)

Abstract Mitochondria, the main provider of energy in eukaryotic cells, contains more than 1000 different proteins and is closely related to the development of cells. However, damaged proteins impair mitochondrial function, further contributing to several human diseases. Evidence shows mitochondrial proteases are critically important for protein maintenance. Most importantly, quality control enzymes exert a crucial role in the modulation of mitochondrial functions by degrading misfolded, aged, or superfluous proteins. Interestingly, cancer cells thrive under stress conditions that damage proteins, so targeting mitochondrial quality control proteases serves as a novel regulator for cancer cells. Not only that, mitochondrial quality control proteases have been shown to affect mitochondrial dynamics by regulating the morphology of optic atrophy 1 (OPA1), which is closely related to the occurrence and progression of cancer. In this review, we introduce mitochondrial quality control proteases as promising targets and related modulators in cancer therapy with a focus on caseinolytic protease P (ClpP), Lon protease (LonP1), high‐temperature requirement protein A2 (HrtA2), and OMA‐1. Further, we summarize our current knowledge of the advances in clinical trials for modulators of mitochondrial quality control proteases. Overall, the content proposed above serves to suggest directions for the development of novel antitumor drugs.
The journey of CAR-T therapy in hematological malignancies
Authors: Junru Lu, Guan Jiang
Journal: Molecular Cancer (2022)

Abstract Chimeric antigen receptor T (CAR-T) cells therapy has revolutionized the treatment paradigms for hematological malignancies, with multi-line therapy-refractory patients achieving durable complete remissions (CR) and relatively high objective response rate (ORR). So far, many CAR-T products, such as Kymriah, Yescarta and Tecartus, have been developed and got the unprecedented results. However, some patients may relapse afterwards, driving intense investigations into promoting the development of novel strategies to overcome resistance and mechanisms of relapse. Notable technical progress, such as nanobodies and CRISPR-Case9, has also taken place to ensure CAR-T cell therapy fully satisfies its medical potential. In this review, we outline the basic principles for the development and manufacturing processes of CAR-T cell therapy, summarize the similarities and differences in efficacy of different products as well as their corresponding clinical results, and discuss CAR-T immunotherapy combined with other clinical effects of drug therapy.
New Federal Incentives for Diversity in Clinical Trials
Authors: Thomas J. Hwang, Otis W. Brawley
Journal: New England Journal of Medicine (2022)

Too often, the clinical trials that provide the evidence on which drug approvals and medical practices are based fail to offer adequate support for medical decision making, because they include inappropriately narrow and homogeneous study populations.The Journal has begun requiring investigators to report on the representativeness of their study participants, but what are the next steps?In this Perspective Roundtable,
Potential therapeutic targets for age-related macular degeneration: The nuclear option
Authors: Mayur Choudhary, Goldis Malek
Journal: Progress in Retinal and Eye Research (2022)

The functions and activities of nuclear receptors, the largest family of transcription factors in the human genome, have classically focused on their ability to act as steroid and hormone sensors in endocrine organs. However, they are responsible for a diverse array of physiological functions, including cellular homeostasis and metabolism, during development and aging. Though the eye is not a traditional endocrine organ, recent studies have revealed high expression levels of nuclear receptors in cells throughout the posterior pole. These findings have precipitated an interest in investigating the role of these transcription factors in the eye as a function of age and ocular disease, in particular age-related macular degeneration (AMD). As the leading cause of vision impairment in the elderly, identifying signaling pathways that may be targeted for AMD therapy is of great importance, given the lack of therapeutic options for over 85% of patients with this disease. Herein we review this relatively new field and recent findings supporting the hypothesis that the eye is a secondary endocrine organ, in which nuclear receptors serve as the bedrock for biological processes in cells vulnerable in AMD, including retinal pigment epithelial and choroidal endothelial cells, and discuss the therapeutic potential of targeting these receptors for AMD.
Neoantigen reactive T cells correlate with the low mutational burden in hematological malignancies
Authors: Sunil Kumar Saini, Staffan Holmberg-Thydén, Anne-Mette Bjerregaard, Ashwin Unnikrishnan, Simon Dorfmüller, Uwe Platzbecker, Irene Tirado-Gonzalez, Halvard Bönig, Daniel El Fassi, Kirsten Grønbæk, John Pimanda, Hind Medyouf, Sine Reker Hadrup
Journal: Leukemia (2022)